Hand foot skin reaction in cancer patients treated with the multikinase inhibitors sorafenib and sunitinib

Background: This study examined clinicopathological findings and management of hand foot skin reaction (HFSR) to sorafenib and sunitinib in a dermatology referral center for cancer-related toxic effects. Patients and methods: We identified 12 patients who developed HFSR in a 1-year period (2007). Medical records and histological specimens were investigated for clinicopathological data and results on management. Results: We identified 12 patients developing HFSR on treatment with sorafenib (83%) or sunitinib (17%). Majority presented with grade 3 (75%) HFSR and a median Skindex score of 43. Biopsies in seven patients showed horizontal layers of keratinocyte necrosis, which correlated to time of drug exposure: early (<30 days from initiation) leading to stratum granulosum-spinosum alterations and late (≥30 days) resulting in stratum corneum pathology. Treatment with topical urea singly (n = 3), plus tazarotene (n = 7), or fluorouracil (n = 2) resulted in ≥2 grade improvement in the majority of patients (58%), with five patients (42%) improving one grade (P = 0.007). Median Skindex score at follow-up was 32 (P = 0.22). Conclusions: There are unique clinicopathological characteristics of HFSR due to the multikinase inhibitors that correlate with time of agent initiation. Treatment with topical agents having keratolytic, antiproliferative, and anti-inflammatory properties showed benefit.